Binders of Chondroitin Sulfate Proteoglycan (CSPG4) Polypeptides

Abstract

This document provides methods and materials involved in binding a binder (e.g., an antibody, antigen binding fragment, antibody domain, CAR, cell engager, and/or ADC) to a CSPG4 polypeptide. For example, binders (e.g., antibodies, antigen binding fragments, antibody domains, CARs, cell engagers, and/or ADCs) that bind to a CSPG4 polypeptide and methods and materials for using one or more such binding molecules to treat a mammal (e.g., a human) having cancer are provided.

1 . An antibody comprising:
 (i) a heavy chain variable domain or region comprising the amino acid sequences set forth in SEQ ID NO:1 (or SEQ ID NO:1 with one, two, or three amino acid additions, deletions, or substitutions), SEQ ID NO:2 (or SEQ ID NO:2 with one, two, or three amino acid additions, deletions, or substitutions), and SEQ ID NO:3 (or SEQ ID NO:3 with one amino acid addition, deletion, or substitution), and a light chain variable domain or region comprising the amino acid sequences set forth in SEQ ID NO:9 (or SEQ ID NO:9 with one, two, or three amino acid additions, deletions, or substitutions), SEQ ID NO:10 (or SEQ ID NO:10 with one, two, or three amino acid additions, deletions, or substitutions), and SEQ ID NO:11 (or SEQ ID NO:11 with one, two, or three amino acid additions, deletions, or substitutions); or   (ii) a heavy chain variable domain or region comprising the amino acid sequences set forth in SEQ ID NO:17 (or SEQ ID NO:17 with one, two, or three amino acid additions, deletions, or substitutions), SEQ ID NO:18 (or SEQ ID NO:18 with one, two, or three amino acid additions, deletions, or substitutions), and SEQ ID NO:19 (or SEQ ID NO:19 with one, two, or three amino acid additions, deletions, or substitutions), and a light chain variable domain or region comprising the amino acid sequences set forth in SEQ ID NO:25 (or SEQ ID NO:25 with one, two, or three amino acid additions, deletions, or substitutions), SEQ ID NO:26 (or SEQ ID NO:26 with one, two, or three amino acid additions, deletions, or substitutions), and SEQ ID NO:27 (or SEQ ID NO:27 with one, two, or three amino acid additions, deletions, or substitutions).   
     
     
         2 . An antigen binding fragment comprising:
 (i) a heavy chain variable domain or region comprising the amino acid sequences set forth in SEQ ID NO:1 (or SEQ ID NO:1 with one, two, or three amino acid additions, deletions, or substitutions), SEQ ID NO:2 (or SEQ ID NO:2 with one, two, or three amino acid additions, deletions, or substitutions), and SEQ ID NO:3 (or SEQ ID NO:3 with one amino acid addition, deletions or substitution), and a light chain variable domain or region comprising the amino acid sequences set forth in SEQ ID NO:9 (or SEQ ID NO:9 with one, two, or three amino acid additions, deletions, or substitutions), SEQ ID NO:10 (or SEQ ID NO:10 with one, two, or three amino acid additions, deletions, or substitutions), and SEQ ID NO:11 (or SEQ ID NO:11 with one, two, or three amino acid additions, deletions, or substitutions); or   (ii) a heavy chain variable domain or region comprising the amino acid sequences set forth in SEQ ID NO:17 (or SEQ ID NO:17 with one, two, or three amino acid additions, deletions, or substitutions), SEQ ID NO:18 (or SEQ ID NO:18 with one, two, or three amino acid additions, deletions, or substitutions), and SEQ ID NO:19 (or SEQ ID NO:19 with one, two, or three amino acid additions, deletions, or substitutions), and a light chain variable domain or region comprising the amino acid sequences set forth in SEQ ID NO:25 (or SEQ ID NO:25 with one, two, or three amino acid additions, deletions, or substitutions), SEQ ID NO:26 (or SEQ ID NO:26 with one, two, or three amino acid additions, deletions, or substitutions), and SEQ ID NO:27 (or SEQ ID NO:27 with one, two, or three amino acid additions, deletions, or substitutions).   
     
     
         3 . The antibody of  claim 1 , wherein said antibody comprises the ability to bind to a CSPG4 polypeptide. 
     
     
         4 . The antibody of  claim 1 , wherein said antibody comprises said heavy chain variable domain or region of said (i). 
     
     
         5 . The antibody of  claim 4 , wherein said heavy chain variable domain or region comprises an amino acid sequence having at least 90 percent identity to the amino acid sequence set forth in SEQ ID NO:8. 
     
     
         6 . The antibody of  claim 1 , wherein said antibody comprises said light chain variable domain or region of said (i). 
     
     
         7 . The antibody of  claim 6 , wherein said light chain variable domain or region comprises an amino acid sequence having at least 90 percent identity to the amino acid sequence set forth in SEQ ID NO:16. 
     
     
         8 . The antibody of  claim 1 , wherein said antibody comprises said heavy chain variable domain or region of said (ii). 
     
     
         9 . The antibody of  claim 8 , wherein said heavy chain variable domain or region comprises an amino acid sequence having at least 90 percent identity to the amino acid sequence set forth in SEQ ID NO:24. 
     
     
         10 . The antibody of  claim 1 , wherein said antibody or said antigen binding fragment comprises said light chain variable domain or region of said (ii). 
     
     
         11 . The antibody of  claim 10 , wherein said light chain variable domain or region comprises an amino acid sequence having at least 90 percent identity to the amino acid sequence set forth in SEQ ID NO:32. 
     
     
         12 . The antibody of  claim 1 , wherein said antibody is a monoclonal antibody. 
     
     
         13 . The antibody of  claim 1 , wherein said antibody is an scFv antibody. 
     
     
         14 . (canceled) 
     
     
         15 . (canceled) 
     
     
         16 . A chimeric antigen receptor comprising an antigen binding domain, a hinge, a transmembrane domain, and one or more signaling domains, wherein said antigen binding domain comprises an antibody of  claim 1 . 
     
     
         17 . A cell comprising a chimeric antigen receptor of  claim 16 . 
     
     
         18 . The cell of  claim 17 , wherein said cell is a T cell, a stem cell, or an NK cell. 
     
     
         19 . A cell engager comprising a first antigen binding domain, a linker, and a second antigen binding domain, wherein said first antigen binding domain comprises an antibody of  claim 1 . 
     
     
         20 . The cell engager of  claim 19 , wherein said second antigen binding domain binds to a polypeptide expressed on the surface of T cells. 
     
     
         21 . The cell engager of  claim 20 , wherein said polypeptide expressed on the surface of T cells is a CD3 polypeptide. 
     
     
         22 . The cell engager of  claim 20 , wherein said second antigen binding domain binds to a polypeptide expressed on the surface of NK cells. 
     
     
         23 . The cell engager of  claim 22 , wherein said polypeptide expressed on the surface of NK cells is a CD16a polypeptide. 
     
     
         24 - 26 . (canceled) 
     
     
         27 . A nucleic acid comprising a nucleic acid sequence encoding at least part of an antibody of  claim 1 . 
     
     
         28 . A nucleic acid comprising a nucleic acid sequence encoding a chimeric antigen receptor of  claim 16 . 
     
     
         29 . (canceled) 
     
     
         30 . (canceled) 
     
     
         31 . A host cell comprising a nucleic acid of  claim 27 . 
     
     
         32 . A host cell that expresses a chimeric antigen receptor of  claim 16 . 
     
     
         33 . (canceled) 
     
     
         34 . An antibody-drug conjugate (ADC) comprising an antigen binding domain covalently linked to a drug, wherein said antigen binding domain comprises an antibody of  claim 1 . 
     
     
         35 . The ADC of  claim 34 , wherein said drug is selected from the group consisting of calicheamicin, monomethyl auristatin E (MMAE), emtansine (DM1), and an exatecan derivative (Dxd). 
     
     
         36 . A composition comprising an antibody of  claim 1 . 
     
     
         37 - 41 . (canceled) 
     
     
         42 . A method of treating a mammal having cancer, wherein said method comprises administering, to said mammal, a composition of  claim 36 . 
     
     
         43 . The method of  claim 42 , wherein said mammal is a human. 
     
     
         44 . The method of  claim 42 , wherein said cancer is a CSPG4 +  cancer. 
     
     
         45 . The method of  claim 44 , wherein said CSPG4 +  cancer is CSPG4 +  ovarian cancer. 
     
     
         46 . (canceled) 
     
     
         47 . A method for binding a binding molecule to a CSPG4 polypeptide, wherein said method comprises contacting said CSPG4 polypeptide with an antibody or an antigen binding fragment of  claim 1 . 
     
     
         48 - 52 . (canceled)